2023 marks the 50th anniversary of the discovery of the association between HLA-B27 and ankylosing spondylitis. Two groups, one from University of California, Los Angeles and the other from Westminster Hospital in London, UK, independently published this finding in 1973 (Schlosstein et al. NEJM 1973, Brewerton et al. Lancet 1973). The rest is history. Importantly though, it was the association with AS that was reported in 1973. HLA-B27 itself had been discovered a few years earlier by the Norwegian immunologist Eric Thorsby who performed human-to-human skin graft experiments to induce novel HLA-specific antisera. Originally named FJH (the initials of the HLA-B27 positive skin donor), it was labeled W27 at the 4th International Histocompatibility Workshop in 1970 and renamed HLA-B27 in a later nomenclature update.
Fast forward 50 years. Even though we still don’t fully understand the mechanisms of the association, we might be finally moving closer. Several recent studies reported an enrichment of a conserved TCR beta motif in CD8+ T cells in HLA-B27+ AS patients confirming similar findings with CD8+ T cell clones from the 1990s. The most recent study from Chris Garcia’s group at Stanford University used single-cell TCR-seq to study CD8+ T cells in synovial fluid and aqueous humor from HLA-B27+ patients with AS and acute anterior uveitis (Yang et al. Nature 2022). Clonally expanded TCR alpha and beta pairs were identified and expressed as recombinant T cell receptors to screen for HLA-B27 restricted peptides using a technique called yeast display. Several candidate peptides derived from microbial and endogenous protein were identified that await further study. Could it be that the arthritogenic peptide hypothesis ultimately turns out to be correct?
To learn more about HLA-B27 and its role in SpA, please join us at the 2023 SPARTAN Annual Meeting in May in Cleveland, OH. The meeting planning committee led by Marina Magrey has created an exciting program that will include a session devoted to the HLA-B27 anniversary. The scientific meeting will be preceded by a one-day Spondyloarthritis Review Course (formerly known as Trainee Symposium). This name change reflects our intention to broaden the target audience of this traditional educational activity to non-trainees including rheumatology advanced practice providers.
Registration for the 2023 Annual Meeting is open. See you in Cleveland!
Joerg Ermann, MD